Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma

Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)-6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL-2 family proteins (BCL-2, BCL-XL, BAX and MCL-1) were also investigated. In addition, the RPMI 8226 cell line (IL-6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 micromol/l). BCL-2, BCL-XL and MCL-1 showed decreased expression in depsipeptide-treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.     

Synergistic effects of rmhTRAIL and 17-AAG on the proliferation and apoptosis of multiple myeloma cells

ABSTRACT

Objective: This study aimed to investigate synergistic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 -allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and apoptosis of multiple myeloma (MM) cells.

Methods: MTT assays evaluated inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and treatment durations on the proliferation of RPMI8226 and U266 cells. The half maximal inhibitory concentration was calculated using OriginPro7.5. Synergistic effects of rmhTRAIL and 17-AAG on apoptosis of MM cells were detected using flow cytometry at 24 and 48?h post-treatment. To evaluate synergistic effects of rmhTRAIL and 17-AAG, the Q-value was calculated using King's formula.

Results: rmhTRAIL exhibited significant inhibitory effects on the proliferation of RPMI8226 cells in a dose- and time-dependent manner (>50%), whereas U266 cells were not sensitive to rmhTRAIL (<50%). 17-AAG inhibited the proliferation of RPMI8226 and U266 cells in a dose-dependent manner (>80%). Significant synergistic effects of rmhTRAIL and 17-AAG on the proliferation of RPMI8226 cells were revealed (Q-value?>?1.15), whereas synergistic effects were not evident on the proliferation of U266 cells (Q-value?<?1.15). rmhTRAIL and 17-AAG exhibited significant synergistic effects on apoptosis of RPMI8226 and U266 cells (Q-value?>?1.15).

Conclusion: The combined application of rmhTRAIL and 17-AAG revealed favorable synergistic effects in the treatment of MM.     

脑源性神经营养因子及其受体在多发性骨髓瘤细胞中的表达及意义

目的 研究多发性骨髓瘤（MM）脑源性神经营养因子（BDNF）及其受体的表达水平在MM发生与发展中的作用。方法 RT-PCR法、Western blot法检测人类MM细胞系（HMCLs）RPMI 8226、U266、KM3细胞BDNF及其受体P75^NTR和TrkB的表达;ELISA法检测HMCLs BDNF的分泌水平;免疫组织化学染色法检测MM患者骨髓活检切片中BDNF和TrkB的表达。采用四唑盐比色法观察BDNF对MM细胞增殖的影响;用改良的Boyden小室法观察BDNF对MM细胞迁移影响。结果 HMCLs不仅表达和分泌BDNF蛋白,也表达其高亲和力酪氨酸激酶受体TrkB。骨髓活检15例MM患者有12例瘤细胞BDNF阳性表达（80％）,15例TrkB阳性表达（100％）;而9例对照组正常造血细胞仅有2例和4例弱阳性表达。研究表明BDNF以剂量和时间依赖性方式促进MM细胞的增殖,并可明显促进MM细胞的迁移。结论 MM中存在着BDNF及其受体TrkB的异常表达,BDNF可能通过促进MM细胞的增殖、迁移参与MM的病理生理进程。     

Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Objectives

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients.

Methods

The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed.

Results

5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO.

Discussion

Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.     

多发性骨髓瘤合并侵袭性真菌感染的临床特点及易感因素分析

目的 了解多发性骨髓瘤(MM)患者合并侵袭性真菌感染(IFI)的临床特点及易感因素.方法 回顾357例在我院住院诊治的MM患者,记录是否合并 IFI、一般临床资料、并发病、抗真菌治疗以及疗效和毒副作用.结果 44例(12.3%)患者在治疗过程中曾发生IFI,其中3例(6.8%)为确诊病例,8例(18.1%)为临床诊断,33例(75.0%)为拟诊.44例患者中,10例(22.7%)处于诱导化疗时出现真菌感染;4例(9.1%)为平台期;27例(61.4%)处于疾病进展状态;3例(6.8%)在行自体造血干细胞移植的过程中发生真菌感染.感染部位以肺部最常见,占50.O%.两性霉素B、伏立康唑、伊曲康唑、卡泊芬净、氟康唑的有效率分别为83.3%、75.O%、78.9%、75.O%和57.1%.各种抗真菌药物之间疗效比较差异无统计学意义(P=0.493).根据多因素分析,合并糖尿病(P=0.035,OR 2.527,95%CI 1.005～6.052),接受透析治疗(P=0.022,OR 2.768,95%CI 1.161～6.600)、粒细胞缺乏持续时间超过1周(P:0.019,OR 3.215,95%CI 1.200～7.407),之前是否使用广谱抗生素治疗(P=0.009,OR 3.350,95%CI 1.353～8.295),是否使用氟达拉滨(P=0.001,OR 4.669,95%CI1.813-12.023)差异有统计学意义.结论 MM患者是侵袭性真菌感染的高危人群,肺部是其最常见的感染部位,4种抗真菌药的疗效相当,合并糖尿病、化疗同时接受透析治疗、长时间粒细胞缺乏、广谱抗生素的应用、以及含有氟达拉滨的治疗是MM合并IFI的易感因素.     

4′,5,7-三羟基异黄酮抗骨髓瘤细胞增殖机制的研究

目的：为了研究4′,5,7-三羟基异黄酮（genistein,Gen）是否能抑制人多发性骨髓瘤（multipule myeloma,MM）细胞株XG1的增殖,研究Gen处理骨髓瘤细胞后B细胞淋巴瘤/白血病-2基因（bcl-2）、bcl-xl、细胞周期蛋白D1（cyclin D1）、细胞间黏附因子1（ICMA-1）基因表达变化及骨髓瘤细胞中核转录因子κB（NF-κB）表达的变化。方法：利用体外培养人MM细胞株XG1,依据剂量梯度分别给予Gen,用噻唑蓝染色法（MTT）观察不同药物浓度的Gen对MM细胞的增殖影响;5、10、15μg/mLGen与溶剂对照组分别作用XG1细胞48h后,半定量逆转录聚合酶链反应（RT-PCR）法检测XG1细胞bcl-2、bcl-xl、细胞周期蛋白D1、ICMA-1基因表达;应用5μg/mLGen处理XG1细胞,用免疫组织化学法观察Gen处理前后细胞内NF-κB的表达情况。结果：Gen作用XG1细胞48h,随浓度增加,细胞增殖逐渐下降;5、10、15μg/mLGen处理组mRNA的表达均低于溶剂对照组（P〈0.05）,伴随Gen处理浓度逐渐增加,bcl-2、bcl-xl、细胞周期蛋白D1、ICMA-1基因mRNA的表达逐渐下降;Gen能够使NF-κB在XG1细胞内重新分布,胞浆内出现NF-κB表达,胞核内NF-κB表达下降。结论：Gen可能通过下调骨髓瘤细胞核中NF-κB的表达来抑制bcl-2、bcl-xl、细胞周期蛋白D1、ICMA-1基因mRNA的表达,进而抑制骨髓瘤细胞的增殖、黏附、转移。     

沙立度胺联合MP化疗方案治疗多发性骨髓瘤23例

目的：观察沙立度胺联合MP方案治疗多发性骨髓瘤的疗效及其不良反应。方法：确诊的多发性骨髓瘤患者23例。沙立度胺-MP方案：沙立度胺自MP方案开始持续给药，每晚睡前口服，剂量从每天100mg开始，每周日剂量递增50mg，至患者不能耐受或最高至每日400mg；MP方案每月1个疗程。结果：部分缓解16例（69．6％），进步4例（17．4％），总有效率为87．0％（20／23）。有效的患者中10例在4周内起效，沙立度胺每天100～400mg，中位剂量每天225mg。常见的不良反应为皮疹、便秘、嗜睡、乏力、头昏、水肿等。结论：沙立度胺加MP方案治疗多发性骨髓瘤不良反应少，耐受性好，且反应率可能提高。     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

目的观察硼替佐米联合地塞米松治疗多发性骨髓瘤(MM)的疗效和不良反应。方法2005年6月至2007年7月收集温州医学院附属第一医院14例MM患者,其中男11例,女3例;年龄52~77岁,平均年龄为65.1岁。第1,4,8和11天给予静脉推注硼替佐米1.3mg/m2;第1~4天,8~11天给予地塞米松20~40mg静脉滴注,每例患者接受1~8个疗程的治疗。采用欧洲骨髓移植协作组(EBMT)标准观察疗效,并按美国国立癌症研究所(NCI)(第3版)CTCAE标准判断不良反应。结果中位随访时间为3.5(1.3~10)个月,12例(86%)患者对治疗有效,其中2例完全缓解,6例患者接近完全缓解,3例部分缓解,1例轻微反应;2例进展。14例患者中10例出现不同程度的乏力,7例出现周围神经病变,腓肠肌酸痛2例,4例出现胃肠道症状,5例血小板减少,1例播散型带状疱疹,1例顽固性低钠血症。均经对症治疗基本缓解。结论硼替佐米联合地塞米松是治疗MM的新的有效治疗方法,不良反应稍多,但经对症治疗及调整用药剂量后均能改善。     

Overexpression of cyclooxygenase-2 in multiple myeloma: association with reduced survival

Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid to prostaglandins. Several studies have shown a relation between angiogenesis and COX-2 expression. Elevated expression of cyclooxygenase-2 (COX-2), however, has not been reported in multiple myeloma (MM) in the literature. The aim of this study is to investigate COX-2 expression in MM as well as its correlation with prognostic factors and estimated survival rates. Immunohistochemical staining of the paraffin-embedded bone marrow biopsy tissues (n = 51) was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz Biotechnology, Santa Cruz, CA). Results were correlated with recognized clinical parameters, which were retrospectively obtained from patients' files. There were 15, 19, and 17 bone marrow biopsy specimens with negative, weak-moderate, and strong COX-2 immunostaining, respectively. According to univariate analysis, beta2-microglobulin, age, stage, COX-2 expression, and serum lactate dehydrogenase levels were significant prognostic factors for survival in patients with multiple myeloma. COX-2 expression, age, and serum lactate dehydrogenase levels (greater than 1x normal level) were significant prognostic factors by multivariate analysis. Kaplan-Meier overall survival estimate of those patients with negative or weak-moderate COX-2 immunoreactivity in myeloma cells was significantly better than that of patients with strong COX-2 immunoreactivity (log-rank chi(2) = 21,43, P < 0.001). COX-2 overexpression was associated with reduced estimated survival. Poor prognostic factors such as LDH, age, and beta2-microglobulin were also correlated with COX-2 expression. Potent, specific COX-2 inhibitors showing evident antiangiogenic and antitumor effects on cancers could provide new therapeutic strategies in the treatment of MM.     

多发性骨髓瘤患者生存因素分析

目的：分析１９７６年５月￣１９９９年１０月３６例多发性骨髓瘤（ＭＭ）患者可能影响生存因素。方法：根据入院时的临床和实验室记录,应用Ｌｏｇｒａｎｋ和ＣＯＸ回归分析对有关因素作单因素和多因素分析,并绘制Ｋａｐｌａｎ－Ｍｅｉｅｒ生存曲线。结果：单因素分析发现ＭＭ患者的生存与年龄、临床分期、骨髓浆细胞百分数（ＢＭＰＣ）、血红蛋白（Ｈｂ）、血清白蛋白（Ａ１ｂ）及化疗结果之间有显著相关性（Ｐ〈０．０５或〈０．     

Technetium-99m 2-methoxy-isobutyl-isonitrile uptake scintigraphy in detection of the bone marrow infiltration in multiple myeloma: correlation with MRI and other prognostic factors

Whole-body scintigraphy with Technetium-99m 2-methoxy-isobutyl-isonitrile (^99mTc-MIBI) has been proposed as a useful method for demonstrating the areas of active bone marrow infiltration in multiple myeloma (MM). In this study, we compared the ^99mTc-MIBI scan with magnetic resonance imaging (MRI), skeletal X-ray survey, and biochemical markers of disease activity in MM to determine its potential in predicting the extension of the disease. Twenty-four myeloma patients had undergone to the ^99mTc-MIBI scan. Only two patients showed negative results in the ^99mTc-MIBI scan; one had clinically active disease, and the other was on remission. MRI was performed to 18 clinically active patients, and 16 of them showed positive myelomatous bone marrow involvement. No significant difference was found between the ^99mTc-MIBI scan and MRI in predicting the extension of bone marrow infiltration in MM (p = 0.11). ^99mTc-MIBI scores were correlated with bone marrow neoplastic plasma cell ratio (p = 0.005), serum paraprotein level (p < 0.001), serum lactate dehydrogenase (p = 0.031), and beta-2 microglobulin (p = 0.045). The ^99mTc-MIBI scan showed disease activity better than the skeletal X-ray survey (x ²  = 5.299, p = 0.021). A significant decrease was found in posttreatment ^99mTc-MIBI scores of the patients with positive overall response (p = 0.016). The ^99mTc-MIBI scan is a noninvasive test that can show the extension of the disease in MM. It seems that the ^99mTc-MIBI scan and MRI show extension and intensity of the myelomatous bone marrow infiltration equally well. The ^99mTc-MIBI scan can be an alternative to MRI when it is not available or if there is any limitations for its usage.     

Analysis of clinical characteristics and prognostic factors of multiple myeloma: a retrospective single-center study of 787 cases

Objective: This study aims to explore the clinical features of multiple myeloma (MM) and the influence of various prognostic factors on survival.

Methods: A retrospective analysis, consisting of clinical characteristics analysis and laboratory examinations, was performed on 787 MM patients. Clinical and laboratory parameters were analyzed by multivariate process and compared across different groups.

Results: Of the 787 patients enrolled (median age, 61 years old, range 29–89 years old), 491 (62.4%) were male. Two most common complaints were bone pain (51.2%) and fatigue (48.0%). Anemia (hemoglobin (Hb) ≤100?g/L in female, Hb ≤110?g/L in male) was present initially in 69.4% patients. IgG was the most common type (46.6%). 52.2% of the patients were diagnosed on stage IIIA according to Durie–Salmon (D–S) system, 44.6% are on stage III according to International Staging System (ISS). Multivariate analysis suggested that age, serum calcium, LDH, percentage of abnormal plasma cells in bone marrow were all independent prognostic factors for OS.

Conclusion: The MM patients in China are relatively younger, have higher rate on stage III according to D–S system. Older age, high serum calcium, high LDH, high percentage of abnormal plasma cells in bone marrow were highly related to poor prognosis.     

Histologic verification of leukemia,myelodysplasia, and multiple myeloma diagnoses in patients in Ukraine, 1987-1998

In preparation for a possible large epidemiological study of radiation-related leukemia in Chernobyl clean-up workers of Ukraine, histologic evaluation of 62 cases of leukemia and related disorders was conducted by a panel of expert hematologists and hematopathologists from the United States, France, and Ukraine. All cases were randomly selected from a surrogate population of men in the general population of 6 regions of Ukraine who were between the ages of 20 and 60 years in 1986 and were reported to have developed leukemia, myelodysplasia, or multiple myeloma between the years 1987 and 1998. The hematologists and hematopathologists on the panel were in agreement with one another and with the previously reported diagnoses and classifications of about 90% of the cases of acute and chronic leukemia in the study. These results suggest that strong reliance can be placed on the clinical diagnoses of acute and chronic forms of leukemia and multiple myeloma that have occurred in Ukrainian Chernobyl clean-up workers providing that the diagnoses are supported by records of the patients having had adequate histologic bone marrow studies. The number of cases in this study with the diagnosis of myelodysplasia, however, was too small to draw firm conclusions.     

CTD方案治疗难治或复发多发性骨髓瘤

目的应用环磷酰胺、沙立度胺及地塞米松(CTD)方案治疗难治或复发多发性骨髓瘤(MM)。方法20例难治或复发MM患者接受沙立度胺,100~200mg/d,口服持续应用;环磷酰胺,200~300mg.m-2.d-1,1~4d,静脉注射;地塞米松,20~40mg/d,1~4d,口服。4周为1个疗程。3个疗程后,若出现疗效或病情稳定则再连续应用3个疗程;若病情进展,则停止治疗。结果3个疗程后,13例(65%)患者显示治疗反应,其中9例患者获部分缓解,4例患者获微小缓解。而5例患者病情稳定,2例进展。对病情未进展的18例患者继续治疗3个疗程后再次评价,则部分缓解13例(65%),获微小缓解5例。结论CTD是一个具有较好治疗前景的方案。     

Enediyne lidamycin induces apoptosis in human multiple myeloma cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase

In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, on two human multiple myeloma (MM) cell lines, U266 and SKO-007, were evaluated. In MTS assay, LDM showed much more potent cytotoxicity than conventional anti-MM agents to both cell lines. The IC₅₀ values of LDM for the U266 and SKO-007 cells were 0.0575 ± 0.0015 and 0.1585 ± 0.0166 nM, respectively, much lower than those of adriamycin, dexamethasone, and vincristine. Mechanistically, LDM triggered MM cells apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in LDM-induced cell death. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed the LDM-induced apoptosis through decreasing the level of cleaved PARP and caspase-3/7. Interestingly, phosphorylation of extracellular signal-related kinase was increased by LDM; conversely, MEK inhibitor synergistically enhanced LDM-induced cytotoxicity and apoptosis in MM cells. The results demonstrated that LDM suppresses MM cell growth through the activation of p38 MAPK and JNK, with the potential to be developed as a chemotherapeutic agent for MM.     

Prognostic significance of the serum phosphorus level and its relationship with other prognostic factors in multiple myeloma

We studied the serum phosphorus (P) level of 110 patients with multiple myeloma (MM) (age range 42–83 years, median 62 years) and evaluated the relationship between that and other prognostic factors. Serum P level significantly correlated with the prognostic factors that are relevant to renal dysfunction: serum creatinine (P<0.00000001), serum β2-microglobulin (P=0.00000088), serum uric acid (P=0.0000014), and corrected serum calcium (cCa P=0.000067). Although it also correlated with the percentage of plasma cells in bone marrow nucleated cells (BMPC%) and the hemoglobin (Hb) and leukocyte counts, the significance was less than for the other four prognostic factors. Serum creatinine, BMPC%, leukocyte count, serum uric acid, bone lesions, β2-microglobulin, and serum cCa were all significantly higher and Hb significantly was lower in the MM patients with hyperphosphatemia (serum P>3.8 mg/dl). The survival time was significantly shorter in these patients (P=0.000087). Multivariate analysis (Cox’s proportional hazards regression model) showed that the serum P level is a significant negative prognostic factor in MM patients.     

持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤的临床疗效观察

目的:观察持续小剂量地塞米松加沙立度胺对难治性多发性骨髓瘤的疗效.方法:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤21例,治疗方法用沙立度胺初始剂量100～200 mg/d,晚上1次顿服,从100 mg开始的患者过2周后加量至200 mg,以后维持在200 mg,地塞米松给予1.5 mg,每天2次口服,二药联合小剂量应用,持续3个月,在后1个半月,地塞米松可减量至1.5 mg,每天1次.3个月后进行化疗1个疗程,3个月为1个周期.结果:2个周期治疗后有6例部分缓解,9例进步,6例无效,其中3例加重,总有效率达71.4%.结论:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤疗效确切,不良反应少.     

Towards a new age in the treatment of multiple myeloma

Multiple myeloma (MM) is an incurable disease characterized by the proliferation of end-stage B lymphocytes (plasma cells, PCs). As a consequence of myeloma growth in the bone marrow, a number of signaling pathways are activated that trigger malignant PC proliferation, escape from apoptosis, migration, and invasion. Thanks to new insights into the molecular pathogenesis of MM, novel approaches aimed at targeting these abnormally activated cascades have recently been developed and others are under study. These strategies include the inhibition of membrane receptor tyrosine kinases, inhibition of the proteasome/aggresome machinery, inhibition of histone deacetylases, inhibition of farnesyltransferases, targeting of molecular chaperones, and others. We will herein review and discuss these novel biological approaches with particular emphasis on those based on biochemical pathways which drive cell signaling. By providing the rationale for innovative therapeutic strategies, the above mechanisms represent targets for new compounds being tested in the management of this disease.     

The pan-histone deacetylase inhibitor CR2408 disrupts cell cycle progression, diminishes proliferation and causes apoptosis in multiple myeloma cells

In view of the fact that histone deacetylases (HDACs) are promising targets for myeloma therapy, we investigated the effects of the HDAC inhibitor CR2408 on multiple myeloma (MM) cells in vitro. CR2408 is a direct pan-HDAC inhibitor and inhibits all known 11 HDACs with a 50% inhibitory concentration (IC(50) ) of 12 nmol/l (HDAC 6) to 520 nmol/l (HDAC 8). Correspondingly, CR2408 induces hyperacetylation of histone H4, inhibits cell growth and strongly induces apoptosis (IC(50) =0.1-0.5 μmol/l) in MM cell lines and primary MM cells. CR2408 leads to fragmentation of cells and induces an accumulation in the subG1 phase accompanied with moderately decreased levels of cyclin D1 and cdk4 and strongly decreased levels of cdc25a, pRb and p53. Interruption of the cell cycle is reflected by inhibition of cell proliferation and is accompanied by decreased phosphorylation of 4E-BP1 and p70S6k. Treatment with CR2408 results in increased protein levels of Bim and pJNK and downregulation of Bad and Bcl-xL and activation of Caspases 3, 8 and 9. Furthermore, as HDAC inhibitors have shown synergism with other drugs, these effects were investigated and synergism was observed for combinations of CR2408 with doxorubicin and bortezomib. In conclusion, we have identified potent anti-myeloma activity for this novel HDAC inhibitor that gives further insights into the biological sequelae of HDAC inhibition in MM.     

多发性骨髓瘤合并肾功能不全38例临床和预后分析

目的研究多发性骨髓瘤合并肾功能不全的临床特点及肾功能可逆性的相关因素和生存相关因素。方法回顾性分析1999-01~2003-12北京协和医院收治的91例初治多发性骨髓瘤及其中38例多发性骨髓瘤合并肾功能不全患者的临床资料。结果91例初治多发性骨髓瘤中有38例(41·8%)合并肾功能不全。合并肾功能不全的患者病程进展更快,贫血更严重,血乳酸脱氢酶(LDH)和β2-微球蛋白(β2-MG)质量浓度更高,以及尿蛋白量更多,同时对化疗的反应更差及生存时间更短。其中34·2%的患者肾功能不全是可逆的,血肌酐和LDH是肾功能可逆的独立预测因素。肾功能可逆患者的生存时间与肾功能正常患者的生存时间比较差异无显著性意义。Cox生存多因素分析发现肾功能可逆性(B=1·294,EXP(B)=3·647,P=0·001)是与生存惟一相关的因素。结论肾功能不全是多发性骨髓瘤常见并发症,相当一部分患者的肾功能可以恢复正常,血肌酐水平和LDH水平是肾功能可逆的重要因素,肾功能可逆性是独立的生存预后因素。